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INTERLEUKIN-1A (IL-1A), IL-1B, IL-1RN, IL-6 AND IL-6R AND PROSTATE CANCER RISK IN AFRICAN AMERICAN AND CAUCASIAN MEN

Appenteng, Kwame Afari (2009) INTERLEUKIN-1A (IL-1A), IL-1B, IL-1RN, IL-6 AND IL-6R AND PROSTATE CANCER RISK IN AFRICAN AMERICAN AND CAUCASIAN MEN. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Prostate cancer incidence and mortality rates continue to be higher among African Americans than Caucasians. While psychosocial factors may explain some of the disparities, the role played by genetic differences in the two racial groups is not so clear. Emerging evidence suggests an important role of chronic or recurrent inflammation in prostate carcinogenesis. Interleukin-1 (IL-1) and IL-6 are inflammatory genes reported to be associated with prostate cancer risk. Interleukin-1 and IL-6 cytokines also decrease bone mineral density (BMD) by inducing osteoclasts to resorb bone matrix. We sought to determine if genotypes of IL-1A, IL-1B, IL-1RN, IL-6 and IL-6R were associated with prostate cancer risk, as well as with selected risk factors, in the two racial groups.We examined allele frequency distributions of polymorphisms in IL-1A, IL-1B, IL-1RN, IL-6 and IL-6R genes in a cross-sectional study of African American and Caucasian men ages 40 to 80 years old. We also assessed the associations of genotypes of these inflammatory genes and the risk of prostate cancer in a case-control study of the two racial groups. Additionally, we evaluated the associations of bone mineral density and prostate cancer in our sample. We found racial differences in minor allele frequencies, as well as in the associations of single nucleotide polymorphisms of inflammatory genes IL-1 and IL-6 and prostate cancer. We also found associations of IL-1 and IL-6 genotypes and prostate cancer. Additionally, we found an inverse association of BMD and prostate cancer in both racial groups. Our findings support a growing body of evidence that chronic or recurrent inflammation play an important role in prostate carcinogenesis, and the possibility of ethnic based differences in susceptibility. Understanding the role of IL-1 and IL-6 genes in the development of prostate cancer is of great public health significance because it will enable their possible use as biomarkers for early detection and prompt intervention, increase our understanding of the molecular biology of the disease, open up new avenues for prevention and treatment, as well as explain some of the observed disparities in the disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Appenteng, Kwame Afarikaa26@pitt.edu, kappenteng@cs.comKAA26
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeissfeld, Joeljwepid@pitt.eduJWEPID
Committee MemberBunker, Clareannbunkerc@edc.pitt.eduBUNKERC
Committee MemberWilson, Johnwilson@nsabp.pitt.eduJWW
Committee MemberFerrell, Robertrferrell@pitt.eduRFERRELL
Date: 29 June 2009
Date Type: Completion
Defense Date: 17 April 2009
Approval Date: 29 June 2009
Submission Date: 7 April 2009
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: cytokine; inflammation; Prostate cancer
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04072009-200629/, etd-04072009-200629
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38
URI: http://d-scholarship.pitt.edu/id/eprint/6865

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